Abstract— Rat brain SAM levels were markedly increased after methionine administration, whereas the convulsant, L‐methionine‐dl‐sulphoximine (MSO), produced a 35 per cent decrease in whole brain content of S‐adenosyl‐L‐methionine (SAM). When methionine was given in combination with MSO, SAM levels were not decreased. Studies on the regional distribution of SAM revealed only a small variation between regions (from 24 nmol/g in midbrain to 49‐5 nmol/g in striatum). SAM levels were reduced by about 50 per cent in the cerebellum, striatum, cortex and hippocampus 3 and 6 h after MSO. It is proposed that abberant cerebral methylation processes may be involved in the genesis of the MSO seizure.

The ability of S-adenosyl-L-homocysteine (AdoHcy) to inhibit biologic transmethylation reactions in vitro has led us to explore the possibility of pharmacologically manipulating AdoHcy levels in vivo and examining the consequences of these alterations on the transmethylation of some biogenic amines. Swiss-Webster mice were injected intraperitoneally with different doses of adenosine (Ado) and D, L-homocysteine thiolactone (Hcy) and were killed at various times thereafter. S-Adenosyl-methionine (AdoMet) and AdoHcy concentrations were determined by using a modified isotope dilution-ion exchange chromatography-high pressure liquid chromatography technique sensitive to less than 10 pmol. Increasing doses of Ado + Hcy (50-1000 mg/kg of each) produced a dose-related increase in blood, liver, and brain AdoHcy levels. At a dose level of 200 mg/kg Ado + Hcy, AdoHcy levels were markedly elevated, with minimal concomitant perturbations of AdoMet. This elevation was maximal 40 min after giving Ado + Hcy, returning to control values within 6 h. Ado + Hcy treatment resulted in decreased activities of catechol-O-methyltransferase, histamine-N-methyltransferase, and AdoHcy hydrolase in vitro. The cerebral catabolism of intraventricularly administered [(3)H]histamine (HA) was decreased in a dose-related manner by Ado + Hcy treatment as evidenced by higher amounts of nonutilized [(3)H]HA in brain, concurrent decreases in [(3)H]methylhistamine formation, and decreases in the transmethylation conversion index. Steady state levels of HA also showed dose-related increases after Ado + Hcy treatment. It is concluded that injections of Ado + Hcy can markedly elevate AdoHcy levels in vivo, which can, in turn, decrease the rate of transmethylation reactions.

Scilliroside and other bufadienolide glycosides in red squill, Urginea marítima (L.) Baker, were identified by isolation, high-performance liquid chromatography and thin-layer chromatography. Scilliroside, the major toxic glycoside, occurs in all plant parts including leaves, flower stalk, scales, and especially the roots and core of this bulbous plant. Other scilla compounds detected include desacetylscilliroside, scillarén A, and the aglycon scillirosidin. A new glucosylscilliroside and a phenolic nonscilla glycoside were also isolated and partially characterized. Scilliroside content of bulbs is highest in late summer after a dormancy period and does not appear to change with age. The scilliroside content of seed-derived varieties differs substantially, indicating a genetic factor affecting toxicant levels in the individual seedling plants. Toxicity of the bulbs is due principally to their content of scilliroside. The 6-acetoxy group of scilliroside contributes substantially to this toxicity.

No abstract

1. m-Xylene (1 g/kg, i.p., 1 h) increased formation of benzo(a)pyrene (BP) mutagenic bay region diols, BP-7,8-diol (66%) and BP-9,10-diol (56%) by rat pulmonary microsomal preparations, while formation of individual BP phenols and quinones was unaltered. 2. m-Xylene administration produced a decrease in cytochrome P450IIB1 activity as measured by pentoxy- and benzyloxy-resorufin O-dealkylation (PROD, BROD), while cytochrome P450IA1 activity, expressed as ethoxyresorufin O-dealkylation (EROD), was unaltered. 3. Pulmonary microsomal epoxide hydrolase activity was also unaltered by m-xylene. 4. In summary, m-xylene alters the relative contribution of P-450 isozymes to BP metabolism resulting in inhibition of BP detoxication and increased production of toxic metabolites.